和癌症(regulationof microrna processing and its implications for development and cancer)

和癌症(regulationof microrna processing and its implications for development and cancer)

ID:18245661

大小:2.93 MB

页数:35页

时间:2018-09-16

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1、RegulationofmicroRNAprocessinganditsimplicationsfordevelopmentandcancerJ.MichaelThomson TheHammondLab1Thomson,J.M.2MicroRNAexpressionprofilesThomsonandHammond,unpublisheddata3EvolutionaryConservedmiRNACluster4miR17-92isConservedinVertebrates5miR-17-92isAmplifiedinLymphomaOta,et.al.,C

2、ancerRes.200464:3087-956Themir17-92clusterresidesinaregionwithknownamplificationsincasesofDLBCL,follicularandmantlecelllymphoma,andseverallungandhead/neckcarcinomasLymphomacelllineswithknownamplificationforC13orf25exhibithighlevelexpressionformiR17-92comparedtocelllineslackingamplifi

3、cation.Allcelllinesexhibitreducedexpressionoflet7familymemberscomparedtocordbloodB-cellsmiR-17-92isAmplifiedinLymphomaHe,etalNature435(7043):828-3320057OverexpressionofmiR-17-19binaMouseModelofHumanLymphoma8ExpressionofmiR17-19bResultsinB-cellLymphomaHe,etalNature435(7043):828-332005

4、9miR-17-92isregulatedbyE2Ftranscriptionfactors10MicroRNAexpressionprofilesThomsonandHammond,unpublisheddata11OncomiR-1andLet-7familyareinverselyexpressedindevelopmentandcancerTumorigenesisDevelopmentThomsonandHammond,unpublisheddataThemicroRNAhypothesisofcancerTumorsdown-regulatemany

5、microRNAstopromotea“stemcell”likestateSelectedmicroRNAs(oncomiRs)areexpressedatahighleveltopromoteproliferationandsuppressapoptosisWhatisthemechanismforwidespreadalterationsingeneExpression?Transcription,processing,turnover?14TranscriptionalreactivationwithmethylaseandHDACInhibitorsr

6、esultsintheactivationof17/313microRNAsAsimilarstudyof15microRNAsoftendown-regulatedinCancerfrom91cancercelllinesrevealedlesionsthatoftendisruptedthesecondarystructureofthepri-miRNA,buthavelittleornoeffectonexpressionGeneticdeletionscanexplainsomecasesofmicroRNAloss,buttheseareoftenli

7、mitedtospecificindividualcases.Anotherpossibilitycouldberegulatedprocessing,asmanymicroRNAsresideintheintronsofcommonhousekeepingmRNAs.Saito,Y.,etalCancerCell2006;Diederichs&HaberCancerRes.2006;Calin,GA.,etalPNAS2002,200415ExonicNon-codingMicroRNAsaretranscribedbyRNAPolymeraseIIIntro

8、nicNon-codin

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